EFFECTS OF ALDRIN ON MEMBRANE FLUIDITY AND ITS IMPLICATIONS FOR THE MECHANISMS OF TOXICITY

There is evidence that aldrin toxicity is initiated at the level of th e cell membrane. Therefore its interaction with membrane components is of significant biochemical interest in efforts to clarify its precise mechanism of action. Thus we have studied the effects of aldrin on th e physical state of model membranes by fluorescence polarization of DP H (1,6-diphenyl-1,3,5-hexatriene) and of its propionic acid derivative DPH-PA, which indicate fluidity changes in the bilayer core and in th e outer regions of the bilayer respectively. Aldrin (100 mu M) increas ed, although to a limited extent, the fluorescence polarization of DPH and DPH-PA in fluid models of egg phosphatidylcholine, implicating a reduced motion of phospholipid acyl chains, i.e. a decrease of fluidit y. In agreement with data for fluid models of egg lecithin, aldrin als o decreased the fluidity in the fluid phase of dimyristoylphosphatidyc holine (DMPC). On the other hand, the fluorescence polarization of DPH and DPH-PA showed that the insecticide increased membrane fluidity in the gel phase of DMPC bilayers. Additionally, the phase transition pr ofiles of DMPC vesicles treated with aldrin were broadened as compared to controls. This indicates that the cooperativity of the transition was affected by the insecticide. Furthermore, aldrin exerted fluidizin g effects i.e. it increased the motion of phospholipid acyl chains, in DMPC bilayers enriched with cholesterol. Therefore, aldrin has specif ic effects on the structural properties of different membrane phases. These changes in fluidity, if also exerted in lipid domains of native membrane, may perturb membrane functions in association with aldrin to xicity. Med Sci Res 26:557-561 (C) 1998 Lippincott Williams & Wilkins.